Acetic Acid → trans 1-(3-amino-cyclopentyl)-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea

HRID 906034Notes

Reaction equation

HRID 906034 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[C@H:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([NH:20][C:21]2[N:22]=[C:23]3[CH:29]=[CH:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:24]3=[N:25][CH:26]=2)=[O:19])[CH2:13]1.NN.CC(O)=O>CN(C=O)C>[NH2:3][C@H:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([NH:20][C:21]2[N:22]=[C:23]3[CH:29]=[CH:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:24]3=[N:25][CH:26]=2)=[O:19])[CH2:13]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 9321HydrazineHCID 86642313HCID 86642313, compound

Product 1

HCID 67431274trans 1-(3-amino-cyclopentyl)-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-ureaYield 68.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Trans 1-[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-cyclopentyl]-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea (0.288 g, 0.50 mmol) was dissolved with heating in DMF (10 mL) and placed in a 45° C. oil bath. The flask was evacuated and refilled with nitrogen three times. Hydrazine (0.16 mL, 5.1 mmol) was added via syringe. After 30 minutes AcOH (0.6 mL) was added and the mixture heated for 30 minutes more before being evaporated. MeOH was added, filtered and the filtrate was evaporated. H2O was added, filtered and the filtrate was evaporated. The residue was purified by reverse phase column chromatography (20-80% MeOH in 0.1% aqueous AcOH) to give trans 1-(3-amino-cyclopentyl)-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea (0.134 g, 60% yield).

Workup

  1. customplaced in a 45° C.
  2. customThe flask was evacuated
  3. additionrefilled with nitrogen three times
  4. temperaturethe mixture heated for 30 minutes more
  5. custombefore being evaporated
  6. additionMeOH was added
  7. filtrationfiltered
  8. customthe filtrate was evaporated
  9. additionH2O was added
  10. filtrationfiltered
  11. customthe filtrate was evaporated
  12. customThe residue was purified by reverse phase column chromatography (20-80% MeOH in 0.1% aqueous AcOH)

Sources & evidence

ORD record
ord-ecfc1c3f0a6e4aeeb46dbe831b753867
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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